Dr.Noori Rheumatologist Dr.Noori Rheumatologist Twenty years ago, medical textbooks said that women with lupus should not get pregnant because of the risks to both the mother and unborn child. Today, most women with lupus can safely become pregnant. With proper medical care you can decrease the risks associated with pregnancy and deliver a normal, healthy baby. Although the presence of SLE does not have a detrimental impact on fertility, active lupus at the time of conception is a predictor of a negative pregnancy outcome. To increase the chances of a happy outcome, however, must carefully plan for pregnancy. the disease should be under control or 6 mounths in remission before conception takes place. Despite the risks associated with pregnancy and perhaps an increased risk of learning disabilities, children born to women with SLE have normal intelligence and development compared with sex- and gestational agematched controls. flares during pregnancy occur in up to 30% of women. Flares that do develop often occur during the first or second trimester or during the first few months following delivery. Most flares, are mild. And you can often treat them with low doses of corticosteroids women with lupus were more likely to have multiple complications of pregnancy, including diabetes, urinary tract infections, and pre- eclampsia. Pregnancy . Women with lupus who become pregnant have a much higher risk of pregnancy-related complications, miscarriage, and premature delivery than women without the disease. the hormone prolactin, which rises during pregnancy, is associated with lupus activity during pregnancy(. Likely other hormonal influences, especially estrogen,) In pregnancy have an excess of renal and hematologic flares, and fewer arthritis flares. Women with SLE who desire to become pregnant should be asked about their pregnancy history, including complications encountered during previous pregnancies, modes of delivery, and fetal outcomes. In women with a history of SLE-related organ damage, such as lupus nephritis and hemolytic anemia, SLE should be quiescent for at least 6 months before conception. Women with severe lung disease (e.g., interstitial lung disease), heart disease(e.g., recent myocardial infarction), or cerebrovascular accident should be advised to avoid pregnancy altogether and perhaps to explore alternatives to childbirth such as surrogacy or adoption. The reason is the high risk of mortality associated with these complications. Severe pulmonary hypertension, for instance, has a risk of mortality in pregnancy that approaches 30%. Preterm delivery . About one out of every three women with lupus delivers preterm. That means before completing 37 weeks of pregnancy. This is more likely in women with preeclampsia, antiphospholipid antibodies, and active lupus. Many women with lupus can have vaginal deliveries. But if the mother or baby is under stress, a cesarean section may be the safest and fastest way to deliver. In lupus patients with a history of avascular necrosis of the hips, a spontaneous vaginal delivery may cause musculoskeletal damage, so that a planned cesarean section is warranted. Markers for pregnancy complications Women with proliferative lupus nephritis had a higher risk of preeclampsia.nephritis Women with hemolytic anemia (a condition in which not enough red blood cells are made in the body) had a higher risk for preterm delivery and preeclampsia. Women with Raynaud's phenomenon had a higher risk for preterm delivery.Raynaud's phenomenon Markers for pregnancy complications Women with antiphospholipid syndrome (a blood disorder that causes abnormal clotting) had a higher risk of miscarriages, especially in the second trimester, slow fetal growth, and preeclampsia. Hypertensive complications. Complications involving high blood pressure can affect up to 20% of pregnant women who have lupus. High blood pressure can be brought on by pregnancy. High blood pressure can also increase risk of preeclampsia.high blood pressureblood pressureHigh blood pressurepreeclampsia Miscarriage. Approximately one out of every five lupus pregnancies ends in miscarriage. Miscarriages are more likely in women with high blood pressure, active lupus, and active kidney disease. Miscarriage can also be the result of antiphospholipid antibodies.Miscarriages tendency to form blood clots in the veins and arteries. That includes those in the placenta. For this reason, it is important to screen for the antibodies. Antiphospholipid.blood clots arteries risk delivery of a preterm infant, specific risks caused by the presence of antiphospholipid and/or anti-Ro (anti-SSA)/anti-La (anti-SSB) antibodies, and the use of certain medications during pregnancy. Signs and symptoms of normal pregnancy that must be differentiated from those of SLE exacerbations include the following: Chloasma versus malar rash Proteinuria secondary to preeclampsia versus proteinuria due to lupus nephritis Signs and symptoms of normal pregnancy that must be differentiated from those of SLE exacerbations include the following: Thrombocytopenia in pregnancy (ie, hemolysis, elevated liver enzyme levels, and low platelet counts syndrome) versus thrombocytopenia of lupus exacerbation (ie, thrombotic thrombocytopenic purpura or idiopathic thrombocytopenic purpura) Pedal edema and fluid accumulation in joints (especially the knees) in the late stages of pregnancy versus the arthritis of SLE Distinguishing changes of normal pregnancy from lupus flares True synovitis does not occur in normal pregnancy and can be related to a lupus flare. Mild anemia and thrombocytopenia are normal variants of pregnancy, but severe anemia and thrombocytopenia may be an indication of an immune-mediated process, such as immune-medicated thrombocytopenia or hemolytic anemia. Distinguishing changes of normal pregnancy from lupus flares The presence of leukopenia and lymphopenia should raise the suspicion of a systemic autoimmune process. A rise in C3 and C4 levels is a normal variation of pregnancy and this can make identifying an SLE flare difficult, so normal complement levels should not automatically be interpreted as an indication of disease quiescence. Double- stranded DNA, however is not affected by pregnancy and can increase when SLE is uncontrolled. MATERNAL AND FETAL COMPLICATIONS DURING PREGNANCY The risk of thrombosis, infection, thrombocytopenia, cesarean section, preterm labor, and preeclampsia is significantly increased in SLE patients compared with healthy women. Laboratory monitoring done monthly includes the complete blood count, Creatinine liver function tests, urinalysis, and a 24 hour urine for creatinine clearance and total protein. It is controversial whether serologic tests are helpful during pregnancy. In normal pregnancy the C3 and C4 should rise. Lupus nephritis and preeclampsia Differentiating between lupus nephritis and preeclampsia can be challenging since both are characterized by proteinuria and hypertension and the two can sometimes be superimposed on each other in the third trimester. Lupus nephritis and preeclampsia Preeclampsia is defined as new-onset systolic blood pressure of more than 140 /90mm Hg setting of proteinuria (more than 300 mg of protein per 24 hours) after the 20th week of pregnancy. Severe preeclampsia is defined as systolic blood pressure higher than 160 mm Hg or diastolic blood pressure higher than 110 mm Hg with proteinuria of more 5 g protein per day in the presence of pulmonary edema, oliguria ,. Distinguishing lupus nephritis from preeclampsia Factor Preeclampsia (20 wk of gestation Timing Restricted to third trimesteroccurs over hours to days Hypertension Always present Double-stranded DNA Normal Complement levels (C3, C4) normal Serum uric acid level Increases History of preeclampsia Increased risk in subsequent pregnancies History of lupus nephritis Increased risk of preeclampsia Active urine sediment No Renal biopsy Not indicated Delivery Rapid resolution of proteinuria and hypertension Distinguishing lupus nephritis from preeclampsia Factor Lupus nephritis Timing Throughout pregnancyoccurs over weeks to months Hypertension Sometimes present Double-stranded DNA Increased Complement levels (C3, C4) Low/normal Serum uric acid level Unchanged (unless in the presence of renal insufficiency History of preeclampsia No impact on subsequent pregnancies History of lupus nephritis increased risk of flare in pregnancy Active urine sediment Yescellular and granular casts Renal biopsy May be indicated Delivery Proteinuria and hypertension do not resolve Antiphospholipid antibodies Antiphospholipid antibodies, including moderate- to high-titer anticardiolipin antibodies (immunoglobulin G or immunoglobulin M), 2-glycoprotein, and/or lupus anticoagulant, are found in up to one third of SLE patients and present management challenges, particularly in the setting of pregnancy. Neonatal lupus Antibodies directed toward anti-Ro and anti-La proteins can cross the placenta and create a syndrome known as neonatal lupus. The most common manifestation is a photosensitive rash that appears in the infant around 4 to 6 weeks after birth and occurs in up to 20% of infants born to mothers with the anti-Ro antibody. Although this can occur as the classic malar/ butterfly rash, more commonly it consists of nonscarring large, circular macules over the face, trunk, and extremities. The rash usually disappears on its own but can be treated with topical corticosteroids Neonatal lupus Hematologic abnormalities including thrombocytopenia and neutropenia, and hepatic abnormalities such as asymptomatic transaminitis can occur in 10% to 15% of cases. These abnormalities often dissipate as the presence of maternal antibodies in the infant diminishes by months 6 to 8 of life. For this reason, routine screening of newborns for these abnormalities is not recommended.. Neonatal lupus The most serious complication of neonatal lupus, however, is congenital heart block, believed to affect approximately 2%-3% of offspring exposed to anti-Ro antibodies. This risk increases up to 20% in subsequent pregnancies following the birth of an infant with anti-Ro antibodyassociated congenital heart block and may be amplified by the coexistence of hypothyroidism and anti-La antibodies- significantly elevated levels of enzymes called membrane-type matrix metalloproteinase-2 (MMP-2) in the cord blood of babies who developed cardiac neonatal lupus compared to those who didn't. cord blood levels of MMP-2 may one day be used to predict which babies with neonatal lupus will go on to develop heart problems. congenital heart block in Neonatal lupus Neonatal lupus Since congenital heart block usually develops between 18 and 24 weeks gestation, some experts recommend serial fetal echocardiography during this period. Premature atrial contractions and even moderate pericardial effusions should be taken seriously, because these may foreshadow the development of congenital heart block. Since congenital heart block usually develops between 18 and 24 weeks gestation, some experts recommend serial fetal echocardiography during this period. Premature atrial contractions and even moderate pericardial effusions should be taken seriously, because these may foreshadow the development of congenital heart block. Neonatal lupus Although the survival rate for infants with neonatal lupus and congenital heart block is 80% at 1 year, the majority of these infants will need the placement of a permanent pacemaker. Neonatal lupus If first- or second-degree heart block is detected, treatment with dexamethasone should be initiated immediately. However, the administration of steroids for prophylactic purposes is not advised, even in women with a history of congenital heart block in the fetus, due to the adverse effects that steroids can have on the fetus (intrauterine growth retardation and preterm birth) Neonatal lupus Maternal hydroxychloroquine therapy has been associated with a reduced risk of cardiac neonatal lupus, and this is another reason it should be continued throughout pregnancy. hydroxychloroquine, are considered safe in breastfeeding mothers. Prednisone is largely metabolized by the placenta, and is unlikely to cause any fetal malformations, but will increase the risk of diabetes and hypertension in the mother. Distinguishing lupus nephritis from preeclampsia Hydroxychloroquine, low-dose corticosteroids, and azathioprine are considered among the safer medication options in pregnancy. Drugs that should not be taken during pregnancy include methotrexate, cyclophosphamide, mycophenolate mofetil, leflunomide, and warfarin. Some drugs need to be stopped months before you try to become pregnantmethotrexate cyclophosphamidemycophenolate mofetil leflunomidewarfarin